7.10  Neuro-Ophthalmic Differential Diagnoses and Aetiologies


Bi-nasal Hemianopia

  1. Dermatochalasis
  2. Tilted discs, Optic disc drusen
  3. Bilateral sectoral retinitis pigmentosa, temporal retinoschisis, vigabatrin toxicity
  4. Chronic raised intra-cranial pressure
  5. Syphilis
  6. Compression of lateral optic nerve / chiasm by an ICA aneurysm

Centrocaecal Scotoma (Bilateral)


  • Toxic
    • Alcohol
  • Hereditary
    • Leber’s hereditary optic neuropathy
  • Optic neuritis
  • Nutritional
    • Vitamin B12 deficiency
  • Glaucoma
    • Acute angle closure glaucoma

Chiasmal Disease

  1. Neoplasia
    1. Pituitary macroadenoma
    2. Craniopharyngioma
      1. Children: Dwarfism, delayed sexual development, obesity
      2. Adults: Visual loss
    3. Meningioma
      1. Tuberculum sellae, sphenoidal ridge
    4. Glioma
  2. Vascular
    1. Aneurysm
    2. CVA
  3. Cystic
    1. Sinus mucocele
  4. Inflammatory
    1. Multiple sclerosis

Gaze Palsies

In most supranuclear motility disease saccades are affected first, then pursuit, then the vestibulo-ocular reflex.

  • Horizontal eye movements
    • Frontal Eye Fields: Generates horizontal saccade to the opposite side
    • Occipital: Generates horizontal pursuit to the same side
    • PPRF: Enacts horizontal gaze to the same side
    • (Ipsilateral CNVI, Contralateral CNIII)
  • Vertical eye movements
    • Generated from the Rostral Interstitial Nucleus of the MLF (riMLF, midbrain) and the Interstitial Nucleus of Cajal (INC)
Aetiology of Gaze Palsies
  1. CVA
  2. Tumour
  3. MS
  4. Infection (encephalitis)
  5. Trauma
  6. Hydrocephalus
  7. Drugs
  8. Conditions causing vertical gaze palsies:
    1. Parinaud’s (dorsal midbrain) syndrome
      1. Young male: Pinealoma, Craniopharyngioma
      2. Young female: MS
      3. Elderly: CVA
  9. Progressive Supranuclear palsy (Steele-Richardson-Olszewski)
Progressive Supranuclear Palsy versus Parkinson’s Disease

Progressive Supranuclear Palsy

Parkinson’s Disease

Mask Like Facies and ↓ Blink Rate

Progressive Supranuclear Palsy

Usually a more worried expression

Parkinson’s Disease


Progressive Supranuclear Palsy

  1. Supranuclear paralysis of down then upgaze / horizontal (slow vertical saccades BUT good Doll’s head)
  2. ± Convergence insufficiency
  3. Eyelid apraxia

Parkinson’s Disease

  1. Ophthalmoplegia is usually a mild feature
  2. Blepharospasm / apraxia lid opening
  3. Convergence insufficiency
  4. Dry eye, blepharitis

Pseudobulbar Palsy

Progressive Supranuclear Palsy

 (early dysarthria / dysphagia)

Parkinson’s Disease


Postural Instability With Falls

Progressive Supranuclear Palsy

 (early, fall back)

Parkinson’s Disease

±  (late, fall forwards)


Progressive Supranuclear Palsy

Parkinson’s Disease


Progressive Supranuclear Palsy

Parkinson’s Disease


Progressive Supranuclear Palsy

Parkinson’s Disease


Progressive Supranuclear Palsy

Worse (death within 10 years)

Parkinson’s Disease



Progressive Supranuclear Palsy


Parkinson’s Disease


Idiopathic Intracranial Hypertension (Pseudotumour cerebri) – Mimics to Exclude

  • Diseases
    • Chronic lung disease / Obstructive sleep apnoea, anaemia, renal failure, hypothyroidism, Addison’s disease
  • Drugs “OATS”
    • Oral contraceptive pill (causes weight gain and dural venous thrombosis)
    • Vitamin A (e.g. acne cream)
    • Tetracyclines
    • Steroids (esp. withdrawal), Cyclosporine

Light-Near Dissociation


  • Adie’s tonic pupil, Argyll-Robertson pupil
  • Bilateral severe loss afferent light input into BE (retinas, ONs, chiasm)
  • CN III aberrant regeneration
  • Dorsal midbrain syndrome, myotonic dystrophy, diabetes


Anisocoria worse in dark – ‘4 P”

  • Pancoast tumour (Horners)
  • ****Prostitute (Argyll Robertson pupil)
  • Pilocarpine
  • Posterior synechiae
  • (Old Adie’s pupil)


Anisocoria worse in light – “4 T”s

  • Tonic pupil
  • Third nerve palsy
  • Tropicamide (dilating drops)
  • Trauma

Myasthenia Gravis

Ocular Myasthenia
  1. Mitochondrial encephalomyopathies (CPEO, Kearns-Sayre, MELAS)
  2. Oculopharyngeal dystrophy (AD)
  3. Thyroid eye disease
  4. CN palsy
  5. Other causes of ptosis
Generalised Myasthenia

Miller Fisher Syndrome (Variant of Guillain-Barré Syndrome)

  • Triad: Ophthalmoplegia + Ataxia + Areflexia.
  • Anti-ganglioside complex antibodies (Anti-GQ1b), ↑ CSF protein

Myotonic Dystrophy

  • Diplopia rare, no fatigue / diurnal variation
  • Myotonic handshake
  • Christmas tree cataracts
  • Frontal balding

Eaton-Lambert Myasthenic Syndrome

  • Ocular / bulbar involvement rare except for ptosis
  • Muscle strength increases after exercise


  • Dilated pupils (doesn’t occur in MG)

Non-Arteritic Anterior Ischaemic Optic Neuropathy - NAION (Risk Factors)

“Disc at risk” (small cup) +

  1. Old age
  2. Atherosclerosis
    1. Hypertension
    2. Nocturnal hypotension (often on awakening)
    3. Hypercholesterolaemia
    4. Diabetes
    5. Smoking
    6. Obesity
  3. Obstructive sleep apnea
  4. Anaemia
  5. Vasculitis
  6. Hyperviscosity
  7. Thrombophilia
  8. Drugs
    1. Sildenafil
    2. Amiodarone
  9. Cataract surgery
    1. Performing cataract surgery when the fellow eye has already had an NAION has an absolute risk of around 50% of causing an NAION in the operated eye
    2. The risk of NAION being caused by cataract surgery in an eye that is “at risk” (but with no history of NAION in the fellow eye) is unclear
  10. Optic disc drusen
Non-Arteritic versus Arteritic Ischaemic Optic Neuropathy

Non-Arteritic (NAAION)

Arteritic (AAION)


Non-Arteritic (NAAION)


Arteritic (AAION)

> 65yrs


Non-Arteritic (NAAION)

Vascular risk factors
No pain

Arteritic (AAION)

May have preceding amaurosis fugax
“GCA” symptoms

Visual Loss

Non-Arteritic (NAAION)

Less severe (mean 6 / 30)

Arteritic (AAION)

More severe (mean CF)

Optic Disc

Non-Arteritic (NAAION)

Sectoral swelling (often superior)
“Disc at risk”

Arteritic (AAION)

Chalky-white (more pallor)
Diffuse swelling
Later cupping


Non-Arteritic (NAAION)


Arteritic (AAION)



Non-Arteritic (NAAION)

Vascular risk factors
Overnight sleep study

Arteritic (AAION)

(FFA: severe choroidal hypoperfusion)
⊕ Temporal artery biopsy


Non-Arteritic (NAAION)

No proven treatment

Arteritic (AAION)

Systemic steroids

Figure 7.10.1
Arteritic Anterior Ischaemic Optic Neuropathy

Optic Atrophy

i. Pseudo
  1. Optic disc drusen
  2. Pseudophakia
  3. Myelinated nerve fibre layer
  4. Optic nerve hypoplasia, disc pit
ii. Real

A) Primary
Without preceding swelling of the optic disc

  1. Following retrobulbar optic neuritis, posterior ischaemic optic neuropathy
  2. Compression (tumour, aneurysm), traumatic optic neuropathy
  3. Hereditary optic neuropathy, retinal dystrophies (e.g. retinitis pigmentosa)
  4. Nutritional optic neuropathy (e.g. B12, folate)
  5. Drug-induced optic neuropathy (e.g. ethambutol, isoniazid, amiodarone, vigabatrin)
  6. Radiation

Pale, flat, well delineated disc

B) Secondary
With preceding swelling of the optic disc

See below - Optic Disc Swelling

White, raised, poorly delineated disc

Pale, flat, well delineated disc

White, raised, poorly delineated disc

Figure 7.10.2 Right Optic Atrophy

Figure 7.10.2
Right Optic Atrophy


  • Advanced glaucoma
  • Traumatic, toxic
  • Radiation, retinal
  • Optic neuritis (demyelinating, infectious, inflammatory, infiltrative)
  • Papilloedema, paraneoplastic
  • Hereditary
  • Ischaemic
  • Compressive
  • Metabolic (DM, MPS)

Optic Disc Cupping

  1. Physiological +
  2. Glaucomatous
  3. Non-glaucomatous
    1. Congenital (optic disc pit, myopia)
    2. Compression
    3. Arteritic Anterior Ischaemic Optic Neuropathy
  4. Toxic (methanol)
Red flags for Non-Glaucomatous Cupping
  1. Acute change in symptoms / signs
  2. Vision
    1. ↓ Visual acuity
    2. Redness / brightness
    3. Colour vision
  3. ON
    1. Pallor of the rim
    2. Asymmetry
  4. HVF
    1. Vertical / junctional defect
    2. Asymmetry
    3. Doesn’t correlate with disc

Optic Disc Swelling

Pseudo-Disc Swelling
  1. Optic disc drusen
  2. Hyperopia
  3. Myelinated nerve fibre layer
  4. Glial remnants (e.g. Bergmeister papilla), congenitally “full” disc
Real Disc Swelling
  • It is impossible to distinguish the cause of optic disc swelling by clinical appearance alone. All patients with disc swelling should be suspected of having papilloedema (optic disc swelling secondary to raised intra-cranial pressure) until proven otherwise. All patients with papilloedema should be suspected of having a space-occupying lesion until proven otherwise


  1. Idiopathic Intracranial Hypertension (diagnosis of exclusion)
  2. Malignant hypertension
  3. Drugs (ethambutol, amiodarone)


  1. Infection
    1. Meningitis
  2. Vascular
    1. Intracranial hypertension
    2. Venous sinus thrombosis
    3. Arterio-venous malformation
  3. Neoplastic
    1. Intracranial tumour
  4. Hydrocephalus
    Local (Unilateral)
  5. Immunological
    1. Optic neuritis (idiopathic, MS, infection)
    2. Posterior uveitis (sarcoidosis, tuberculosis, syphilis)
  6. Vascular
    1. Diabetic papillopathy
    2. CRVO
    3. AION
  7. Neoplastic
    1. Optic nerve glioma
    2. Meningioma
    3. Lymphoma
  8. Physical
    1. ↓ IOP (hypotony)
    2. ↑ IOP (acute glaucoma)
  9. Metabolic
    1. Thyroid eye disease (with compressive optic neuropathy)
  10. Other
    1. Leber Hereditary Optic Neuropathy
Acute versus Chronic


  • Optic nerve function is usually normal (including visual acuity)
  • Hyperaemia
  • Blurring of disc margin
  • Vessel obscuration, dilation, telangiectasia
  • ± Flame haemorrhages, cotton-wool spots, hard exudate, Paton’s lines
  • No spontaneous venous pulsations


  • Abnormal optic nerve function

  • Pallor
  • “Champagne-cork”, gliosis
  • Vessel sheathing, optociliary shunts
  • Refractile (hyaline, lipid) bodies
  • Abnormal optic nerve function
  • Pallor
  • “Champagne-cork”, gliosis
  • Vessel sheathing, optociliary shunts
  • Refractile (hyaline, lipid) bodies

Optic Disc Swelling (Bilateral)

“5 M”s

  • Malignant hypertension
  • Meningitis
  • Mass – tumour, SAH, SDH
  • Meds – OCP, Vitamin A, Tetracyclines, Steroids
  • Morbid obesity - IIH
  • Venous sinus thrombosis
  • Infiltrative – sarcoidosis, leukemia
Figure 7.10.3 Right Optic Atrophy

Figure 7.10.3
Bilateral Optic Disc Swelling

Optic Neuropathy (Causes)


Hereditary optic neuropathy



  • Optic Neuritis – demyelinating, infective, post infectious, inflammatory
  • Ischaemic – AION, PION
  • Granulomatous – sarcoidosis
  • Hereditary – Lebers HON
  • Traumatic
  • Toxic
    • Ethambutol
      • 6% risk at 25mg / kg / d (rare at 15mg / kg)
    • Amiodarone
      • Idiosyncratic, insidious, can progress despite stopping the drug
    • Vigabatrin
      • Idiosyncratic
    • Chloramphenicol
    • Sildenafil
    • Lead
  • Irradiation
  • Compressive


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